Background This study aimed to compare the effect of Clinpro™ White varnish containing 5% sodium fluoride (NaF) and functionalized tricalcium phosphate, MI varnish containing 5% NaF and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and 38% Silver diamine fluoride (SDF) in preventing demineralization of treated white spot lesions (WSLs) in enamel of primary teeth. Methods Forty-eight primary molars with artificial WSLs were allocated into four groups as follows: Group 1: Clinpro white varnish, Group 2: MI varnish, Group 3: SDF, and Group 4: control (no treatment). The three surface treatments were applied for 24 h and then enamel specimens were subjected to pH cycling. Thereafter, the mineral content of specimens was evaluated by Energy Dispersive X-ray Spectrometer and the lesion depth was assessed via Polarized Light Microscope. One-way ANOVA followed by Tukey’s post hoc test were used at p ≤ 0.05 to identify significant differences. Results Insignificant difference in mineral content was observed among treatment groups. Treatment groups exhibited significantly higher mineral content compared to control except for Fluoride (F). MI varnish showed the highest mean calcium (Ca) ion content (66.57 ± 0.63), and Ca/P (2.19 ± 0.11), followed by Clinpro white varnish, and SDF. MI varnish also displayed the highest phosphate (P) ion content (31.46 ± 0.56), followed by SDF (30.93 ± 1.02), and Clinpro white varnish (30.53 ± 2.19). Fluoride content was highest in SDF (0.93 ± 1.18), followed by MI (0.89 ± 0.34) and Clinpro (0.66 ± 0.68) varnishes. Significant difference in lesion depth was observed among all groups (p < 0.001). The lowest mean lesion depth (µm) was found in MI varnish (226.23 ± 44.25) which was significantly lower than Clinpro white varnish (285.43 ± 44.70), SDF (293.32 ± 46.82), and control (576.69 ± 42.66). Insignificant difference in lesion depth was found between SDF and Clinpro varnish. Conclusions In primary teeth, WSLs treated with MI varnish displayed better resistance to demineralization compared to WSLs treated with Clinpro white varnish and SDF.